Damien wrote:
> As I understand it, the telomeres are reset during nuclear transfer.
> Dolly's were 20% shorter than you'd expect in a beast of her age at the time,
This statement doesn't make any sense to me. If telomeres are "reset", then
you would expect them to be the same length as an average newborn.
I agree (though I haven't got references handy) that the impression
seems to be that in cloned animals the telomeres are shorter and
that would imply they are not being completely "reset". Its an
open question in my mind whether telomere resetting occurs in
the germ cells or after the egg-sperm fusion. If some fraction
of the reset process occurs in either of those two situations,
then you aren't going to get the desired result with nuclear
transfer from adult cells into denucleated eggs.
> I'm not so sure; since most of the original TTAGGGs are lopped during
> normal fetal development, surely you'd expect much more depletion than
> that if her telomeres hadn't been somewhat repaired.
Hmmmm.... this remans an undecided problem IMO. Telomerase remains
active to some extent in any quasi-stem cells. The question is whether
or not the cells that produce viable clones are to some extent such
viable stem cells. Intestinal crypt cells, which I believe were the
been the source of the nuclei for Dolly, do have stem-cell like
properties since they are dividing on a daily-to-weekly basis.
If they didn't have telomerase active then would hit the Hayflick
limit in the first couple of years of your life.
Perhaps Harvey wrote:
> The cells of cloned mice show no signs of premature aging despite being
> copied through six generations, according to a new study. In fact, some of
> the cells showed signs of getting younger.
PLEASE, do not compare mechanisms of aging in mice with mechanisms
of aging in sheep with mechanisms of aging in humans. Mice have *much*
longer telomeres than humans do. Their cells are also much easier to
transform into cancerous cells than human cells are. Short telomeres
are an anti-cancer (and pro-"aging") program only in species that have
had to develop such programs. Mice, and to a lesser extent sheep, do
not live long enough to need as many redundant cancer-prevention programs
and so the length of their telomeres may have much less significance
than it does in humans.
My take -- unless you reset human telomere length to the normal newborn
length in cloned cells (or adult stem cells), you are going to be starting
with a pre-aged program. If you *do* reset telomere length in cloned
cells from embryos, all bets are off because those cells will not have
gone through the selection process that deletes programs that are
developmentally defective. If you *do* reset telomere length in cloned
cells from adults, then you have a program that has certainly accumulated
an unknown mutational load (and may therefore be slanted towards a
pre-cancerous state). The cells you *should* be using are those
from newborn infants, say from umbilical cords, where you know they
produced a viable human but haven't accumulated a mutational load
from years of living in a hazardous environment.
Robert
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